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SUMMARY of PRODUCT CHARACTERISTICS for Lovastatin

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SUMMARY of PRODUCT CHARACTERISTICS for Lovastatin SUMMARY OF PRODUCT CHARACTERISTICS for Lovastatin Mylan tablets 1 NAME OF THE MEDICINAL PRODUCT Lovastatin Mylan 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Lovastatin 20 mg and 40 mg For a full list of excipients see section 6.1. 3 PHARMACEUTICAL FORM Tablets 20 mg: Pale blue, octagonal tablets marked “LV/20” on one side and “G” on the other, with score-line on one side. 40 mg: Green, octagonal tablets marked “LV/40” on one side and “G” on the other, with score-line on one side. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Severe cases of hypercholesterolaemia when dietary treatment does not have an adequate effect. 4.2 Posology and method of administration The patient should be placed on a standard cholesterol-lowering diet before being given lovastatin. This diet should be continued during treatment with lovastatin. Any cause for secondary hypercholesterolemia should be excluded before initiation of treatment. HYPERCHOLESTEROLEMIA: The initial dose is generally 20 mg per day, given as a single dose with the evening meal. It has been shown that single daily doses given with the evening meal are more effective than the same dose given with breakfast, possibly because cholesterol synthesis takes place mainly at night. Patients with mild to moderate hypercholesterolemia may be treated with an initial dose of 10 mg lovastatin. Any dosage adjustments should be made at intervals of at least 4 weeks. A maximum of 80 mg should be given daily in a single dose or divided into 2 doses taken with breakfast and the evening meal. Two daily doses would appear to be more effective than one daily dose. The dosage of lovastatin should be reduced if LDL-cholesterol levels drop below 75 mg/dL (1.94 mmol/L), or if total serum cholesterol concentrations fall below 140 mg/dL (3.6 mmol/L). CONCOMITANT TREATMENT Lovastatin is effective alone or in combination with bile-acid sequestrants. Page 1 of 11 In patients being given cyclosporine, danazol, gemfibrozil, other fibrates or lipid-lowering doses (≥ 1 g/day) of niacin at the same time as lovastatin, the maximum recommended dose is 20 mg/day. In patients taking amiodarone or verapamil concomitantly with lovastatin, the dose of lovastatin should not exceed 40 mg/day (see section 4.4. Special warnings and precautions for use Myopathy/Rhabdomyolysis and 4.5. Interactions with other medicinal products and other forms of interaction) DOSAGE IN RENAL INSUFFICIENCY Since lovastatin does not undergo significant renal excretion, moderate renal insufficiency does not necessitate any dosage reduction. In patients with severe renal failure (creatinine clearance <30 ml/min) dosages over 20 mg/day should be carefully considered, and, if necessary, should be commenced with caution (see section 4.4. Special warnings and precautions for use Myopathy/Rhabdomyolysis and 5.0 Pharmacological properties). USE IN CHILDREN AND ADOLESCENTS (< 18 YEARS): The use of lovastatin in children is not recommended, as safety and efficacy studies have not been established. USE IN THE ELDERLY In a controlled trial of the treatment of patients in the over-sixty age group, the effects appeared to be identical to those in the remainder of the population and there was no marked increase in frequency of clinical or laboratory adverse findings. 4.3 Contraindications Hypersensitivity to lovastatin or to any of the excipients of the medicinal product. Active liver disease or unexplained persistently elevated serum transaminase levels. Cholestasis Myopathy Concomitant administration of potent CYP3A4 inhibitors (itraconazole, ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone). Concomitant treatment with delavirdine, verapamil and amiodarone. Pregnancy and lactation (see section 4.6). Alcoholism 4.4 Special warnings and precautions for use Myopathy/Rhabdomyolysis: Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above 10X the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. - The risk of myopathy/rhabdomyolysis is increased by concomitant use of lovastatin with the following: Potent inhibitors of CYP3A4, e.g., mibefradil (a calcium antagonist of the tetralol type), itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, or nefazodone, particularly with higher doses of lovastatin (see Page 2 of 11 section 4.5. Interaction with other medicinal products and other forms of interaction, CYP3A4 Interactions and 5.2. Pharmacokinetic properties). Lipid-lowering drugs that can cause myopathy when given alone: Gemfibrozil, other fibrates, or lipid-lowering doses (_1 g/day) of niacin, particularly with higher doses of lovastatin (see section 4.5. Interaction with other medicinal products and other forms of interaction, Interactions with lipid-lowering drugs that can cause myopathy when given alone and 5.2. Pharmacokinetic properties). Cyclosporine or danazol particularly with higher doses of lovastatin. (see section 4.5. Interaction with other medicinal products and other forms of interaction, Other drug interactions and 5.2. Pharmacokinetic properties). Other drugs: Amiodarone or Verapamil: The risk of myopathy/rhabdomyolysis is increased when either amiodarone or verapamil is used concomitantly with higher doses of a closely related member of the HMG-CoA reductase inhibitor class (see section 4.5. Interaction with other medicinal products and other forms of interaction, Other drug interactions). Fusidic Acid: The risk of myopathy may be increased when fusidic acid is used concomitantly with a closely related member of the HMG-CoA reductase inhibitor class (see section 4.4. Special warnings and special precautions for use, Myopathy/Rhabdomyolysis and 5.2. “Pharmacokinetic properties”). HMG-CoA inhibitors and antifungal medicinal products, which are azole derivatives, inhibit cholesterol synthesis at different points in the synthesis chain. Patients who are receiving cyclosporin treatment should have lovastatin therapy withdrawn if systemic fungicide treatment with an azole derivative is necessary. Patients who are not receiving cyclosporin treatment should be carefully monitored if systemic fungicide treatment with an azole derivative is necessary. Lovastatin treatment must be temporarily interrupted or withdrawn in patients who have a condition which predisposes them to the development of renal failure, such as a serious acute infection, hypotension, major surgery, trauma, a severe metabolic, endocrine or electrolyte balance disorder or uncontrolled epilepsy. - As with other HMG-CoA reductase inhibitors, the risk of myopathy/rhabdomyolysis is dose related. In a clinical study (EXCEL) in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4933 patients randomized to lovastatin 20-40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily. Creatine Kinase measurement: Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of any plausible alternative cause of CK increase as this makes value interpretation difficult. If CK levels are significantly elevated at baseline (> 5xULN), levels should be re-measured within 5 to 7 days later to confirm the results. Before the treatment: All patients starting therapy with lovastatin, or whose dose of lovastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. Clinicians should prescribe statins with caution in patients with pre-disposing factors for rhabdomyolysis. In order to establish a reference baseline value, a creatine kinase (CK) level should be measured before starting statin treatment in the following situations: - Elderly (age >70 years) Page 3 of 11 - Renal impairment - Uncontrolled hypothyroidism - Personal or familial history of hereditary muscular disorders - Previous history of muscular toxicity with a statin or fibrate - Alcohol abuse In such situations the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended. If a patient has previously experiences a muscle disorder on a fibrate or a statin, treatment with a different member of the class should only be initiated with caution. If CK levels are significantly elevated (> 5xULN) at baseline, treatment should not be started. Whilst on treatment: If muscular pain, weakness or cramps occur whilst a patient is receiving treatment with a statin, their CK levels should be measured. If these levels are found, in the absence of strenuous exercise, to be significantly elevated (>5xULN), treatment should be stopped. If muscular symptoms are severe and cause daily discomfort, even if CK levels are elevated to ≤ 5xULN, treatment discontinuation should be considered. If myopathy is suspected for any other reason, treatment should be discontinued. If symptoms resolve and CK levels return to normal, then re-introduction of the statin or introduction of an alternative statin may be considered at the lowest dose and with close monitoring. Therapy with lovastatin should be temporarily stopped a few days prior to elective major surgery and when any major medical
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